This proposal is based on the application of concepts from basic research on the cell surface and gamete interaction to the clinical problem of immune infertility. Anti-sperm antibodies might lead to infertility in vivo in a variety of ways. Proposed mechanisms include (1) sperm aggulutination, (2) sperm cytotoxicity in the presence of complement, (3) inhibition of cervical mucus penetration, (4) inhibition of discrete steps in gamete interaction, and (5) enhancement of phagocytosis of sperm. Our first goal is to test one of these proposed mechanisms using the guinea pig as an animal model. We will test the hypothesis that anti-sperm antibodies can block fertility in vivo by blocking function of two specific sperm surface antigens required in guinea pig sperm-egg interaction. Since surface antigens of human sperm that function in gamete interaction have not been identified, this hypothesis cannot currently be tested with human sperm. To remedy this situation, our second aim is to identify at least some of the human sperm surface antigens that function in gamete interaction. The third, related goal is to biochemically identify the human sperm surface antigens recognized in individuals with suspected immune infertility. This study will answer to what degree the anti-sperm antibodies from different individuals recognize diverse or common sperm surface antigens. Antigens recognized in common by sera from all patients or groups of patients will be identified. A collection of monoclonal antibodies will be produced that recognizes these common auto- and iso-antigens of the sperm surface. The monoclonal antibodies will be useful for structural characterization of individual auto- and iso-antigens. Also the monoclonal antibody collection to the common antigens could be used in new, highly specific and sensitive tests for diagnosis of immune infertility. In the long term, the common auto-antigens could be purified using the monoclonal antibodies. The purified antigens could be used for treatment in a sub-group of auto-immune men. Purified sperm surface antigens could be added to the ejaculate to absorb out the auto-antibodies thus preventing their binding to sperm.